This grant represents a revised proposal for the study of T cell clonality in multiple sclerosis cerebrospinal fluid by analysing rearrangement patterns of the T cell receptor genes. The studies outlined in the previous grant of peripheral blood and family genetic studies have been deleted from the proposal. New data since submission of the original proposal has been obtained demonstrating oligoclonal T cells in the spinal fluid of an MS patient. In addition, brain tissue has been obtained at an autopsy from a patient in whom T cells were cloned prior to the patient's death. This study will focus on oligoclonal T cells in the spinal fluid of multiple sclerosis patients according to the following specific aims: 1) to what extent are cerebrospinal fluid, oligoclonal T cell populations found in patients with chronic progressive multiple sclerosis? 2) are oligoclonal T cell populations found in early relapsing-remitting patients? 3) do CSF T cell clones reflect the population of T cells in the plaque of MS brain? and 4) what are the functional properties of oligoclonal T cell populations?